Is DRC1 p.Phe417fs (c.1251del) pathogenic?

DRC1 p.Phe417fs (c.1251del) is classified Likely pathogenic in DRC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-08-06). Very rare (popmax 6.84e-05%); Associated with primary ciliary dyskinesia 21.

What condition is associated with DRC1 p.Phe417fs (c.1251del)?

DRC1 p.Phe417fs (c.1251del) is associated with primary ciliary dyskinesia 21, spermatogenic failure 80 (ClinVar).

How common is DRC1 p.Phe417fs (c.1251del) in the general population?

DRC1 p.Phe417fs (c.1251del) is very rare (popmax 6.84e-05%) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DRC1 p.Phe417fs

c.1251del · VCV4974974

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

primary ciliary dyskinesia 21

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP 0.54, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,890 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DRC1
Protein: p.Phe417fs
Coding: c.1251del
MANE Select: NM_145038
Type: Deletion
Location: chr2:26444801 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.44 · 1 PDB
Residue 417: a UniProt-annotated variant site (in spgf80); a UniProt-annotated variant site (in cild21)

Full DRC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 21 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: spermatogenic failure 80

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DRC1 p.Ser659fs Pathogenic ★★ same condition
DRC1 p.Arg694fs Uncertain significance ★★ same condition
DRC1 p.Leu167_Leu168insTer Pathogenic ★ same condition
DRC1 p.Met634fs Likely pathogenic ★ same condition
DRC1 p.Tyr189fs Pathogenic ★ same condition
DRC1 p.Gln118Ter Pathogenic/Likely pathogenic ★★ same condition
DRC1 p.Gln337Ter Pathogenic/Likely pathogenic ★★ same condition
DRC1 p.Gln37fs Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/drc1-p-phe417fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown